Combined treatment with dipeptidyl peptidase-4 inhibitor (sitagliptin) and angiotensin-II type 1 receptor blocker (losartan) suppresses progression in a non-diabetic rat model of steatohepatitis.

• Material Type: 博士論文
• Title: Combined treatment with dipeptidyl peptidase-4 inhibitor (sitagliptin) and angiotensin-II type 1 receptor blocker (losartan) suppresses progression in a non-diabetic rat model of steatohepatitis.
• Author/Editor: Okura, Yasushi; Namisaki, Tadashi; Moriya, Kei; Kitade, Mitsuteru; Takeda, Kosuke; Kaji, Kosuke; Noguchi, Ryuichi; Nishimura, Norihisa; Seki, Kenichiro; Kawaratani, Hideto; Takaya, Hiroaki; Sato, Shinya; Sawada, Yasuhiko; Shimozato, Naotaka; Furukawa, Masanori; Nakanishi, Keisuke; Saikawa, Soichiro; Kubo, Takuya; Asada, Kiyoshi; Yoshiji, Hitoshi
• Author Heading: Okura, Yasushi; Namisaki, Tadashi; Moriya, Kei; Kitade, Mitsuteru; Takeda, Kosuke; Kaji, Kosuke; Noguchi, Ryuichi; Nishimura, Norihisa; Seki, Kenichiro; Kawaratani, Hideto; Takaya, Hiroaki; Sato, Shinya; Sawada, Yasuhiko; Shimozato, Naotaka; Furukawa, Masanori; Nakanishi, Keisuke; Saikawa, Soichiro; Kubo, Takuya; Asada, Kiyoshi; Yoshiji, Hitoshi
• Publication, Distribution, etc.: John Wiley & Sons, Inc.
• Publication Date: 2016-12-28
• Publication Date (W3CDTF): 2016-12-28
• Alternative Title: ジペプチジルペプチターゼ4阻害剤（シタグリプチン）およびアンギオテンシンⅡ1型受容体遮断薬（ロサルタン）の併用療法は非糖尿病ラットモデルにおける非アルコール性脂肪肝炎の進行を抑制する
• Periodical title: Hepatology research
• No. or year of volume/issue: 47 12
• Volume: 47
• Issue: 12
• Pages: 1317-1328
• ISSN (Periodical Title): ISSN : 1386-6346
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2017-09-27
• Dissertation Number: 乙第1406号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: hepatic fibrogenesis; hepatocarcinogenesis; losartan; non-alcoholic steatohepatitis; sitagliptin
• Target Audience: 一般
• Note (General): type:Thesis; AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of non-diabetic non-alcoholic steatohepatitis (NASH) in a rat model. METHODS: To induce NASH, Fischer 344 rats were fed a choline-deficient L-amino acid-defined diet for 12 weeks. We elucidated the chemopreventive effects of sitagliptin + losartan, especially in conjunction with hepatic stellate cell (HSC) activation, angiogenesis, and oxidative stress, all known to play important roles in the progression of NASH. RESULTS: Sitagliptin + losartan suppressed choline-deficient L-amino acid-defined diet-induced hepatic fibrogenesis and carcinogenesis. The combination treatment exerted a greater inhibitory effect than monotherapy. These inhibitory effects occurred almost concurrently with the suppression of HSC activation, neovascularization, and oxidative stress. In vitro studies showed that sitagliptin + losartan inhibited angiotensin II-induced proliferation and expression of transforming growth factor-β1 and α1 (I)-procollagen mRNA of activated HSC and in vitro angiogenesis, in parallel with the suppression observed in in vivo studies. CONCLUSIONS: The widely and safely used sitagliptin + losartan combination treatment in clinical practice could be an effective strategy against NASH.; 博士（医学）・乙第1406号・平成29年9月27日; © 2016 The Japan Society of Hepatology; Copyright © 2016 John Wiley & Sons, Inc. All Rights Reserved.; This is the pre-peer reviewed version of the following article: Hepatology research [Epub ahead of print] (2016 Dec 28), which has been published in final form at http://dx.doi.org/10.1111/hepr.12860. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.; identifier:Hepatology research Vol.47 No.12 p.1317-1328 (2017 Nov); identifier:13866346; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3381; identifier:Hepatology research, 47(12): 1317-1328
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/hepr.12860
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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